tbuckley/cabot-search huggingface dataset:
Stress-induced β cell early senescence confers protection against type 1 diabetes
Authors: Hugo Lee, Gulcan Semra Sahin, Chien-Wen Chen, Shreyash Sonthalia, Sandra Marín Cañas, Hulya Zeynep Oktay, Alexander T. Duckworth, Gabriel Brawerman, Peter J. Thompson, Maria Hatzoglou, Decio L. Eizirik, Feyza Engin
Journal: Cell Metabolism (2023)

During the progression of type 1 diabetes (T1D), β cells are exposed to significant stress and, therefore, require adaptive responses to survive. The adaptive mechanisms that can preserve β cell function and survival in the face of autoimmunity remain unclear. Here, we show that the deletion of the unfolded protein response (UPR) genes Atf6α or Ire1α in β cells of non-obese diabetic (NOD) mice prior to insulitis generates a p21-driven early senescence phenotype and alters the β cell secretome that significantly enhances the leukemia inhibitory factor-mediated recruitment of M2 macrophages to islets. Consequently, M2 macrophages promote anti-inflammatory responses and immune surveillance that cause the resolution of islet inflammation, the removal of terminally senesced β cells, the reduction of β cell apoptosis, and protection against T1D. We further demonstrate that the p21-mediated early senescence signature is conserved in the residual β cells of T1D patients. Our findings reveal a previously unrecognized link between β cell UPR and senescence that, if leveraged, may represent a novel preventive strategy for T1D.
A new measure of exercise adherence: the ATEMPT (Adherence To Exercise for Musculoskeletal Pain Tool)
Authors: Daniel Leslie Bailey, Annette Bishop, Gareth McCray, Nadine E Foster, Melanie A Holden
Journal: British Journal of Sports Medicine (2023)

Objectives This study aimed to (1) develop a new measure of adherence to exercise for musculoskeletal (MSK) pain (Adherence To Exercise for Musculoskeletal Pain Tool: ATEMPT) based on previously conceptualised domains of exercise adherence, (2) report the content and structural validity, internal consistency, test–retest reliability, and measurement error for the ATEMPT outcome measure in patients managed with exercise for MSK pain. Methods ATEMPT was created using statements describing adherence generated by patients, physiotherapists and researchers, with content validity established. Baseline and retest questionnaires were distributed to patients recommended exercise for MSK pain in 11 National Health Service physiotherapy clinics. Items demonstrating low response variation were removed and the following measurement properties assessed: structural validity, internal consistency, test–retest reliability and measurement error. Results Baseline and retest data were collected from 382 and 112 patients with MSK pain, respectively. Confirmatory factor analysis established that a single factor solution was the best fit according to Bayesian Information Criterion. The 6-item version of the measure (scored 6–30) demonstrated optimal internal consistency (Cronbach’s Alpha 0.86, 95% CI 0.83 to 0.88) with acceptable levels of test–retest reliability (intraclass correlation coefficient 0.84, 95% CI 0.78 to 0.88) and measurement error (smallest detectable change 3.77, 95% CI 3.27 to 4.42) (SE of measurement 2.67, 95% CI 2.31 to 3.16). Conclusion The 6-item ATEMPT was developed from the six domains of exercise adherence. It has adequate content and structural validity, internal consistency, test–retest reliability and measurement error in patients with MSK pain, but should undergo additional testing to establish the construct validity and responsiveness.
CD133+ endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice
Authors: Shimin Sun, Yuan Meng, Mingying Li, Xiaolong Tang, Wenjing Hu, Weiwei Wu, Guo Li, Qiuxiang Pang, Wengong Wang, Baohua Liu
Journal: Nature Aging (2023)

Abstract The stem cell theory of aging dictates that a decline in the number and/or function of stem cells causes tissue degeneration and aging; however, it still lacks unequivocal experimental support. Here, using lineage tracing and single-cell transcriptomics, we identify a population of CD133 + bone marrow-derived endothelial-like cells (ELCs) as potential endothelial progenitor cells, which contribute to tubular structures in vitro and neovascularization in vivo. We demonstrate that supplementation with wild-type and young ELCs respectively restores neovascularization and extends lifespan in progeric and naturally aged mice. Mechanistically, we identify an upregulation of farnesyl diphosphate synthase (FDPS) in aged CD133 + ELCs—a key enzyme in isoprenoid biosynthesis. Overexpression of FDPS compromises the neovascularization capacity of CD133 + ELCs, whereas FDPS inhibition by pamidronate enhances neovascularization, improves health measures and extends lifespan in aged mice. These findings highlight stem cell-based strategies for the treatment of progeria and age-related pathologies.
Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens
Authors: Francesco Maura, Eileen M Boyle, David Coffey, Kylee Maclachlan, Dylan Gagler, Benjamin Diamond, Hussein Ghamlouch, Patrick Blaney, Bachisio Ziccheddu, Anthony Cirrincione, Monika Chojnacka, Yubao Wang, Ariel Siegel, James E Hoffman, Dickran Kazandjian, Hani Hassoun, Emily Guzman, Sham Mailankody, Urvi A Shah, Carlyn Tan, Malin Hultcrantz, Michael Scordo, Gunjan L Shah, Heather Landau, David J Chung, Sergio Giralt, Yanming Zhang, Arnaldo Arbini, Qi Gao, Mikhail Roshal, Ahmet Dogan, Alexander M Lesokhin, Faith E Davies, Saad Z Usmani, Neha Korde, Gareth J Morgan, Ola Landgren
Journal: Nature Cancer (2023)
Most large structural variants in cancer genomes can be detected without long reads
Authors: Zi-Ning Choo, Julie M. Behr, Aditya Deshpande, Kevin Hadi, Xiaotong Yao, Huasong Tian, Kaori Takai, George Zakusilo, Joel Rosiene, Arnaud Da Cruz Paula, Britta Weigelt, Jeremy Setton, Nadeem Riaz, Simon N. Powell, Klaus Busam, Alexander N. Shoushtari, Charlotte Ariyan, Jorge Reis-Filho, Titia de Lange, Marcin Imieliński
Journal: Nature Genetics (2023)

Abstract Short-read sequencing is the workhorse of cancer genomics yet is thought to miss many structural variants (SVs), particularly large chromosomal alterations. To characterize missing SVs in short-read whole genomes, we analyzed ‘loose ends’—local violations of mass balance between adjacent DNA segments. In the landscape of loose ends across 1,330 high-purity cancer whole genomes, most large (&gt;10-kb) clonal SVs were fully resolved by short reads in the 87% of the human genome where copy number could be reliably measured. Some loose ends represent neotelomeres, which we propose as a hallmark of the alternative lengthening of telomeres phenotype. These pan-cancer findings were confirmed by long-molecule profiles of 38 breast cancer and melanoma cases. Our results indicate that aberrant homologous recombination is unlikely to drive the majority of large cancer SVs. Furthermore, analysis of mass balance in short-read whole genome data provides a surprisingly complete picture of cancer chromosomal structure.
Regulatory T cell-derived IL-1Ra suppresses the innate response to respiratory viral infection
Authors: Jason W Griffith, Lucas D Faustino, Victoria I Cottrell, Keshav Nepal, Lida P Hariri, Rebecca Suet-Yan Chiu, Michael C Jones, Amélie Julé, Cem Gabay, Andrew D Luster
Journal: Nature Immunology (2023)
CD3ζ ITAMs enable ligand discrimination and antagonism by inhibiting TCR signaling in response to low-affinity peptides
Authors: Guillaume Gaud, Sooraj Achar, François X P Bourassa, John Davies, Teri Hatzihristidis, Seeyoung Choi, Taisuke Kondo, Selamawit Gossa, Jan Lee, Paul Juneau, Naomi Taylor, Christian S Hinrichs, Dorian B McGavern, Paul François, Grégoire Altan-Bonnet, Paul E Love
Journal: Nature Immunology (2023)
Topological analysis of sharp-wave ripple waveforms reveals input mechanisms behind feature variations
Authors: Enrique R Sebastian, Juan P Quintanilla, Alberto Sánchez-Aguilera, Julio Esparza, Elena Cid, Liset M de la Prida
Journal: Nature Neuroscience (2023)

Abstract The reactivation of experience-based neural activity patterns in the hippocampus is crucial for learning and memory. These reactivation patterns and their associated sharp-wave ripples (SWRs) are highly variable. However, this variability is missed by commonly used spectral methods. Here, we use topological and dimensionality reduction techniques to analyze the waveform of ripples recorded at the pyramidal layer of CA1. We show that SWR waveforms distribute along a continuum in a low-dimensional space, which conveys information about the underlying layer-specific synaptic inputs. A decoder trained in this space successfully links individual ripples with their expected sinks and sources, demonstrating how physiological mechanisms shape SWR variability. Furthermore, we found that SWR waveforms segregated differently during wakefulness and sleep before and after a series of cognitive tasks, with striking effects of novelty and learning. Our results thus highlight how the topological analysis of ripple waveforms enables a deeper physiological understanding of SWRs.
Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens
Authors: Sean R McCutcheon, Adam M Swartz, Michael C Brown, Alejandro Barrera, Christian McRoberts Amador, Keith Siklenka, Lucas Humayun, Maria A Ter Weele, James M Isaacs, Timothy E Reddy, Andrew S Allen, Smita K Nair, Scott J Antonia, Charles A Gersbach
Journal: Nature Genetics (2023)

Abstract Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapies. Here we developed pooled, epigenetic CRISPR screening approaches to systematically profile the effects of activating or repressing 120 transcriptional and epigenetic regulators on human CD8 + T cell state. We found that BATF3 overexpression promoted specific features of memory T cells and attenuated gene programs associated with cytotoxicity, regulatory T cell function, and exhaustion. Upon chronic antigen stimulation, BATF3 overexpression countered phenotypic and epigenetic signatures of T cell exhaustion. Moreover, BATF3 enhanced the potency of CAR T cells in both in vitro and in vivo tumor models and programmed a transcriptional profile that correlates with positive clinical response to adoptive T cell therapy. Finally, we performed CRISPR knockout screens that defined cofactors and downstream mediators of the BATF3 gene network.
Spatial and single-cell profiling of the metabolome, transcriptome and epigenome of the aging mouse liver
Authors: Chrysa Nikopoulou, Niklas Kleinenkuhnen, Swati Parekh, Tonantzi Sandoval, Christoph Ziegenhain, Farina Schneider, Patrick Giavalisco, Kat-Folz Donahue, Anna Juliane Vesting, Marcel Kirchner, Mihaela Bozukova, Christian Vossen, Janine Altmüller, Thomas Wunderlich, Rickard Sandberg, Vangelis Kondylis, Achim Tresch, Peter Tessarz
Journal: Nature Aging (2023)

Abstract Tissues within an organism and even cell types within a tissue can age with different velocities. However, it is unclear whether cells of one type experience different aging trajectories within a tissue depending on their spatial location. Here, we used spatial transcriptomics in combination with single-cell ATAC-seq and RNA-seq, lipidomics and functional assays to address how cells in the male murine liver are affected by age-related changes in the microenvironment. Integration of the datasets revealed zonation-specific and age-related changes in metabolic states, the epigenome and transcriptome. The epigenome changed in a zonation-dependent manner and functionally, periportal hepatocytes were characterized by decreased mitochondrial fitness, whereas pericentral hepatocytes accumulated large lipid droplets. Together, we provide evidence that changing microenvironments within a tissue exert strong influences on their resident cells that can shape epigenetic, metabolic and phenotypic outputs.
Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer
Authors: Peter Kreuzaler, Paolo Inglese, Avinash Ghanate, Ersa Gjelaj, Vincen Wu, Yulia Panina, Andres Mendez-Lucas, Catherine MacLachlan, Neill Patani, Catherine B. Hubert, Helen Huang, Gina Greenidge, Oscar M. Rueda, Adam J. Taylor, Evdoxia Karali, Emine Kazanc, Amy Spicer, Alex Dexter, Wei Lin, Daria Thompson, Mariana Silva Dos Santos, Enrica Calvani, Nathalie Legrave, James K. Ellis, Wendy Greenwood, Mary Green, Emma Nye, Emma Still, Peter Kreuzaler, Simon Barry, Richard J. A. Goodwin, Alejandra Bruna, Carlos Caldas, James MacRae, Luiz Pedro Sório de Carvalho, George Poulogiannis, Greg McMahon, Zoltan Takats, Josephine Bunch, Mariia Yuneva
Journal: Nature Metabolism (2023)

Abstract Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy 1–3 . Consequently, spatially resolved omics-level analyses are gaining traction 4–9 . Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC , a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism 10,11 . Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B 5 ) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.
Percutaneous Endoscopic Necrosectomy of Walled-Off Necrosis in Post-ERCP Pancreatitis
Authors: G. Lauri, M. Di Stasi, G. Marinone, P. G. Arcidiacono, S. Russo, R. Conigliaro, G. Aragona
Journal: Endoscopy (2023)

Aims We describe a case report of post-ERCP acute necrotizing pancreatitis with walled-off necrosis (WON) treated with percutaneous endoscopic necrosectomy (PEN).
Same session Endoscopic Ultrasound and ERCP experience at a Tertiary Hospital in Ireland
Authors: M. Elsiddig, M. J. Tracey, S. Sengupta, J. Keohane, N. Iqbal, S. Patchett, D. Cheriyan
Journal: Endoscopy (2023)

Aims Same session EUS and ERCP has the potential to streamline patient investigation and therapy, and to avoid the risk associated with ERCP if biliary pathology is not seen at EUS. We assessed the utility of same session EUS and ERCP in patients referred to our hospital.
Searching for a reference range of pancreatic strain histogram EUS elastography: a pilot study
Authors: C. Laurenza, S. Mazza, B. Elvo, C. Verga, S. Soro, A. Drago, R. Grassia
Journal: Endoscopy (2023)

Aims Strain histogram (SH) EUS-elastography is a semi-quantitative elastographic technique. Defining a pancreatic SH reference range would be useful for early diagnosis of pancreatic parenchymal diseases, mainly early chronic pancreatitis (CP). The study aimed at determining a SH reference range in patients without clinical, radiological, and ultrasonographic evidence of pancreatic disease.
Endoscopic intermuscular dissection of rectal T1 cancer with adaptive traction: use of the additional loops to improve traction directly on the circular muscular layer
Authors: L. J. Masgnaux, J. Grimaldi, J. Rivory, T. Wallenhorst, R. Legros, J. Jacques, P. Mathieu
Journal: Endoscopy (2023)

Abstract Text Endoscopic R0 resection rate for T1 cancers harboring focal invasive patterns is far from perfect on the vertical margin. Recently, Endoscopic intermuscular dissection (EID) was described to get a free vertical margins by dissecting deeper, between the two muscular layers. This approach is feasible in the rectum where the two layers are thick combines the benefits of maintaining the rectal longitudinal muscle and dissecting deeper to get clear free vertical margins when deep submucosa is invaded. To facilitate intermuscular space exposure, as described in ESD, traction seems useful. We describe here an adaptive traction device, (A-TRACT, Hospices Civils de Lyon, France), that could be helpful in this situation [1] [2] [3] [4] [5].
Abdominal computed tomography predictors of technical success of endoscopic ultrasound-guided gallbladder drainage
Authors: A. Cominardi, D. Colombi, E. Michieletti, G. Adenike Adebanjo, G. Aragona
Journal: Endoscopy (2023)

Aims Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) was not always technically feasible. Our study aim was to evaluate abdomen computed tomography (CT) predictors of EUS-GBD technical success (TS).
Ileal B lymphoma of the marginal zone EUS guided fine needle biopsy diagnosis, Case report
Authors: C. Santos Cotes, A. Martins Pinto da Costa, B. Agudo Castillo, E. Santos Pérez, C. Esteban Fernández-Zarza, F. Valentin Gomez, A. Oro Coello, M. González-Haba Ruiz
Journal: Endoscopy (2023)

Abstract Text Primary small intestinal lymphoma is a rare condition, accounting for 15–20% of gastrointestinal lymphomas. Small intestinal marginal zone B cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) is an even less common disease accounting for about 15–30% of primary small bowel lymphomas. There are only a few reported cases of ileal MALT lymphomas, which are more frequent in symptomatic patients and with advanced endoscopic findings. This is the first reported case of EUS-guided biopsy diagnosis of an ileal lymphoma.
Counter-traction with the ProdiGI Traction Magnet facilitates colorectal ESD and can improve patient outcomes
Authors: M. Ayoub, S. Nagl, A. Probst, H. Messmann, A. Ebigbo
Journal: Endoscopy (2023)

Aims Endoscopic submucosal dissection (ESD) is a challenging procedure for resection of early neoplasias. Countertraction can improve access to the submucosal layer and facilitate ESD. We aimed to evaluate the ProdiGI Traction magnet for colorectal ESD.
Efficacy evaluation of Hemostatic powder (UI-EWD) for reduction of re-bleeding rate in patients treated with endoscopic therapy for lower gastrointestinal hemorrhage
Authors: J. Shin, B. Cha, J. S. Park, K. S. Kwon, H. K. Kim
Journal: Endoscopy (2023)

Aims A novel endoscopic hemostatic powder (UI-EWD/Nexpowder, Nextbiomedical, Incheon, South Korea) was applied for the control of Acute gastrointestinal bleeding (GIB). Although UI-EWD has been demonstrated to be effective in hemostasis in upper-GIB, it is still unclear in lower-GIB. The aim of this study was to evaluate the hemostatic efficacy and safety of UI-EWD applied to Lower-GIB.
Clinical outcome of Novel Technology for Colorectal Submucosal Dissection: preliminary analysis for polyp surface and fibrosis with the procedural time
Authors: Z. Tsiamoulos, S. Zeidan, M. Abbas, K. Hills, S. El Kady, N. Bagla, S. Mangam, J. Sebastian
Journal: Endoscopy (2023)

Aims The clinical outcomes of ESD performed using Speedboat RS2/SRS2 (a novel multi-modality device with bipolar radio-frequency(BRF) cutting & microwave (MWC) coagulation)
The role of small bowel capsule endoscopy as a diagnostic tool in isolated complex perianal disease
Authors: I. Avni-Biron, J. E. Ollech, E. Toth, A. Nemeth, G. Wurm Johansson, S. Hagai, R. Margalit Yehuda, U. Kopylov, I. Dotan, H. Yanai
Journal: Endoscopy (2023)

Aims Isolated complicated perianal disease (cPD) might be the sole representation of Crohn’s disease (CD). We aimed to evaluate the impact of small bowel capsule endoscopy (SBCE) as a diagnostic tool for CD in this population.
Clinical impact of the implementation of in-hospital on-call in the management of upper digestive bleeding
Authors: M. Albert, G. Espin Marti, O. Miquel, E. Fort, E. Guarner, D. Busquets, A. Gispert, B. Oliveras, C. Lopez, C. Huertas
Journal: Endoscopy (2023)

Aims The timing of gastroscopy execution in UGB is still controversial; the main scientific societies recommend its performance in the first 24 hours. The implementation of an in-hospital gastroenterology shift could mean an optimization of the time until endoscopy, meaning a greater number of endoscopic treatments, thus leading to a reduction in hospital stay and/or mortality. Our purpose is the analysis of the clinical impact of the implementation of a in-hospital on-call GI system in the management of UGB [1] [2] [3] [4] ([Fig. 1]).
Usefulness of digital pancreatoscopy in the diagnosis of pancreatic cancer. A safety and efficacy pilot study
Authors: M. García Campos, R. Mansilla, N. Alonso, C. Satorres, P. López-Muñoz, V. Lorenzo-Zúñiga García, L. Argüello, M. Bustamante-Balén, V. Pons
Journal: Endoscopy (2023)

Aims Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatoscopy with biopsies could be an option for early diagnosis in these patients. The aim of this study was to assess applicability, efficacy, and safety parameters of pancreatoscopy with biopsies in patients with chronic pancreatitis [1] [2].
Ultrasound-guided needle biopsy fluorescence spectroscopy with quantitative fluorescence endoscopy for response monitoring in patients with esophageal cancer after neoadjuvant chemoradiotherapy using bevacizumab-800CW
Authors: I. Schmidt, A. M. Van Der Waaij, G. Kats-Ugurlu, F. A. Dijkstra, J. W. Haveman, B. Van Etten, D. J. Robinson, W. Nagengast
Journal: Endoscopy (2023)

Aims Ultrasound guided needle biopsy (USNB) reflectance spectroscopy potentially enables assessment of lymph nodes and all esophageal wall layers. This pilot study evaluates the clinical impact of USNB fluorescence spectroscopy using bevacizumab-800CW for the identification of residual tumor in patients with esophageal cancer.
New concept of colonoscopy assisted by microwave-based accessory device: first clinical experience
Authors: M. G. Fernández-Esparrach, O. Ortiz, O. Sendino, S. Rivadulla, J. Sanahuja, G. Martínez-Pallí, A. Garrido, L. M. Neira, R. Sont, J. Llach, M. Pellisé, M. Guardiola
Journal: Endoscopy (2023)

Aims Microwave imaging has demonstrated to detect polyps based on their dielectric properties in ex-vivo colon tissues and in-vivo porcine model. The aim of this study is to evaluate the feasibility and safety of microwave-based colonoscopy for diagnosis of polyps in humans [1] [2].
Performance of linked color imaging compared to conventional white light imaging in endoscopic diagnosis of Helicobacter pylori infection: A systematic review and meta-analysis
Authors: J. G. Lee, I. K. Yoo, S. P. Lee
Journal: Endoscopy (2023)

Aims Recognizing Helicobacter pylori (H. Pylori) infection during endoscopy is important because it can lead to confirmatory testing. Linked color imaging (LCI) is one of the image enhancement techniques that can improve the detection of gastrointestinal lesions. The purpose of this systematic review and meta-analysis was to evaluate the diagnostic performance of LCI compared to conventional white light imaging (WLI) in endoscopic diagnosis of H. pylori infection.
EUS-guided portal pressure gradient measurement: our preliminary experience
Authors: R. Romero-Castro, I. Carmona-Soria, V. A. Jimenez-Garcia, P. Fernandez-Alvarez, P. Cordero-Ruiz, M. Tous-Romero, A. Gutierrez-Domingo, M. Rodriguez-Tellez, A. Caunedo-Alvarez
Journal: Endoscopy (2023)

Methods Patients referred to a tertiary center for EUS-PPG. We used a 25G dedicated needle (EchoTip Insight), used as previously reported [1].